HATFIELD, England, July 31, 2014 /PRNewswire/ --
FOR EU MEDIA ONLY: NOT FOR SWISS MEDIA
Accelerated Review Demonstrates the Importance of
Lenvatinib for This Therapeutic Area
The European Medicines Agency (EMA) has approved Eisai's request
for accelerated assessment of the investigational oral multiple
receptor tyrosine kinase (RTK) inhibitor lenvatinib, for the
treatment of patients with progressive radioiodine-refractory,
differentiated thyroid cancer (RR-DTC). Lenvatinib is expected to
be filed imminently and could become a first in a new class of
tyrosine kinase inhibitors.
Thyroid cancer is the most common endocrine
malignancy.[1] In Europe alone, over 50,000 cases of thyroid
cancer were diagnosed in 2012.[2] Although treatment is
possible for most types of thyroid cancer, there remains an unmet
need for treatment options once the disease has progressed.
Lenvatinib is an oral multiple receptor tyrosine kinase (RTK)
inhibitor with a novel binding mode that selectively inhibits the
kinase activities of vascular endothelial growth factor receptors
(VEGFR), in addition to other proangiogenic and oncogenic
pathway-related RTKs including fibroblast growth factor receptors
(FGFR), the platelet-derived growth factor (PDGF) receptor PDGFRα,
KIT and RET that are involved in tumour proliferation. This
potentially makes lenvatinib a first-in-class treatment, especially
given that it simultaneously inhibits the kinase activities of FGFR
as well as
VEGFR.[3],[4],[5]
Lenvatinib received orphan drug designation (ODD) for the treatment
of follicular and papillary thyroid cancer from the European
Commission in April 2013.
"We are delighted that lenvatinib will undergo accelerated
assessment by the EMA. The EMA recognises that RR-DTC is a
challenging disease to treat and there is an urgent need for
effective treatment options. At time of filing we will be another
step closer to providing an innovative therapy to people with
advanced thyroid cancer," said Gary
Hendler, President & CEO Eisai EMEA and President, Eisai
Oncology Global Business Unit.
The EU marketing authorisation application will be based on the
results of the Phase III SELECT (Study of (E7080)
LEnvatinib in Differentiated Cancer of the
Thyroid) trial of lenvatinib which showed that, progression
free survival (PFS) with lenvatinib was extended significantly
compared to placebo (Hazard Ratio (HR)=0.21, [99% CI, 0.14-0.31];
p<0.0001). The median PFS with lenvatinib and placebo were 18.3
months and 3.6 months, respectively.[6]
The SELECT study was a multicentre, randomised, double-blind,
placebo-controlled Phase III study to compare the PFS of patients
with RR-DTC and radiographic evidence of disease progression within
the prior 13 months, treated with once-daily, oral lenvatinib
versus placebo. Secondary endpoints of the study included overall
response rate (ORR), overall survival (OS) and safety. The study
enrolled 392 patients in over 100 sites in Europe, North and South America and Asia and was conducted by Eisai in
collaboration with the SFJ Pharmaceuticals Group. Eisai hopes to
receive file application in the next few months.
The development of lenvatinib underscores Eisai's human
health care mission, the company's commitment to innovative
solutions in disease prevention, cure and care for the health and
wellbeing of people worldwide. Eisai is committed to the
therapeutic area of oncology and addressing the unmet medical needs
of patients and their families.
Notes to Editors
Lenvatinib (E7080)
Lenvatinib, discovered and developed by Eisai, is an oral
multiple receptor tyrosine kinase (RTK) inhibitor with a novel
binding mode that selectively inhibits the kinase activities of
vascular endothelial growth factor receptors (VEGFR), in addition
to other proangiogenic and oncogenic pathway-related RTKs including
fibroblast growth factor receptors (FGFR), the platelet-derived
growth factor (PDGF) receptor PDGFRα, KIT and RET that are involved
in tumour
proliferation.[7],[8]
This potentially makes lenvatinib a first-in-class treatment,
especially given that it simultaneously inhibits the kinase
activities of FGFR as well as VEGFR. It is currently under
investigation as a treatment for thyroid, hepatocellular carcinoma
(Phase III), non-small cell lung cancer (Phase II) and other solid
tumour types.
About
SELECT [6]
The SELECT (Study of (E7080) LEnvatinib in
Differentiated Cancer of the Thyroid) study was a
multicentre, randomised, double-blind, placebo-controlled Phase III
study to compare the PFS of patients with RR-DTC and radiographic
evidence of disease progression within the prior 13 months, treated
with once-daily, oral lenvatinib (24mg) versus placebo. The study
enrolled 392 patients in over 100 sites in Europe, North and South America and Asia and was conducted by Eisai in
collaboration with the SFJ Pharmaceuticals Group.
Participants were stratified by age (≤65, >65 years), region
and ≤1 prior VEGFR-targeted therapies and randomised 2:1 to either
lenvatinib or placebo therapy (24mg/d, 28-d cycle). The primary
endpoint was PFS assessed by independent radiologic review. The
secondary endpoints of the study included overall response rate
(ORR), overall survival (OS) and safety. Rates of complete response
were 1.5% (4 patients) for the lenvatinib group and zero in the
placebo group. The results for partial response were 63.2% (165
patients) in the lenvatinib group and 1.5% (2 patients) in the
placebo arm. The median exposure duration was 13.8 months for
lenvatinib and 3.9 months for placebo and the median time to
response for lenvatinib was 2.0 months. Median OS has not yet been
reached.
The five most common lenvatinib treatment-related adverse events
(TRAEs) of any grade were hypertension (67.8%), diarrhea (59.4%),
decreased appetite (50.2%), weight loss (46.4%) and nausea (41.0%).
TRAEs of Grade 3 or higher (Common Terminology Criteria for Adverse
Events) included hypertension (41.8%), proteinuria (10.0%), weight
loss (9.6%), diarrhoea (8.0%), and decreased appetite (5.4%).
About Thyroid Cancer
Thyroid cancer refers to cancer that forms in the tissues of the
thyroid gland, located at the base of the throat near the
trachea.[9] It is more common in women than in men and
most are in their 40s or 50s at time of diagnosis.
[1] Thyroid cancer is the most
common endocrine malignancy and global figures show that its
incidence has increased significantly over the last 50 years.
[1]
The most common types of thyroid cancer, papillary and
follicular (including Hurthle cell), are classified as
differentiated thyroid cancer (DTC) and account for approximately
90% of all cases.[10] The remaining cases are classified
as either medullary (5-7% of cases) or anaplastic (1-2% of
cases).[11]While most DTC patients are curable with
surgery and radioactive iodine treatment, the prognosis for those
patients who do not respond is poor.[12] There are
limited treatment options for this difficult-to-treat,
life-threatening and treatment-refractory form of thyroid
cancer.[13]
Eisai in Oncology
Our commitment to meaningful progress in oncology research,
built on scientific expertise, is supported by a global capability
to conduct discovery and preclinical research, and develop small
molecules, therapeutic vaccines, and biologic and supportive care
agents for cancer across multiple indications.
About Eisai
Eisai is one of the world's leading research and development
(R&D) based pharmaceutical companies and we define our
corporate mission as "giving first thought to patients and their
families and to increasing the benefits health care provides,"
which we call human health care (hhc).
Eisai concentrates its R&D activities in three key
areas:
- Oncology including: anticancer therapies; tumour regression,
tumour suppression, antibodies, etc
- Neuroscience, including: Alzheimer's disease, epilepsy, pain
and weight management
- Vascular/Immunological reaction including: thrombocytopenia,
rheumatoid arthritis, psoriasis, inflammatory bowel disease
With operations in the U.S., Asia, Europe
and its domestic home market of Japan, Eisai employs more than 10,000 people
worldwide. From its EMEA Knowledge Centre in Hatfield, UK, Eisai
has recently expanded its business operations to include
Europe, the Middle East, Africa, Russia and Oceania (EMEA). Eisai EMEA has
sales and marketing operations in over 20 markets, including
Austria, Belgium, Czech
Republic, Denmark,
Finland, France, Germany, Iceland, Ireland, Italy, the Middle
East, the Netherlands,
Norway, Portugal, Russia, Slovakia, Spain, Switzerland, Sweden, and the United Kingdom.
For further information please visit our web site:
http://www.eisai.co.uk
References
1. Brito J et al. BMJ 2013; 347
2. Thyroid Cancer. International Agency for Research on
Cancer. http://eco.iarc.fr/eucan/Cancer.aspx?Cancer=35 (last
accessed: July 2014)
3. Data on file, Eisai.Co.Ltd
4. Zuccotto F et al. J. Med. Chem. 2010, 53,
2681-2694.
5. Liao et al. Journal of Medicinal Chemistry, 2007,
50;3:409-422
6. Schlumberger M et al. A phase 3, multicenter,
double-blind, placebo-controlled trial of lenvatinib (E7080) in
patients with 131I-refractory differentiated thyroid cancer
(SELECT). ASCO 2014 abstract #E450
7. Matsui J, et al. Clin Cancer
Res 2008;14:5459-65
8. Matsui J, et al. Int J Cancer
2008;122:664-71
9. National Cancer Institute at the
National Institute of Health
http://www.cancer.gov/cancertopics/pdq/treatment/thyroid/Patient/page1/AllPages#1 (last
accessed: July 2014)
10. Cooper DS et al. Thyroid.
2009;19(11):1167-1214
11. Thyroid Cancer Basics. 2011.
http://www.thyca.org
12. Gild M et al. Multikinase inhibitors: a new option for
the treatment of thyroid cancer. Nature Reviews Endocrinology.
2011; 7: 617-624
13. Bible K, et al. Lancet Oncology
2010;11(10):962-972
Job code: Lenvatinib-UK0032
Date of preparation: July 2014